RESUMO
BACKGROUND: Epidemiological studies on predisposing conditions and outcomes of progressive multifocal leukoencephalopathy (PML) cases have been carried out exclusively in high-income countries. We aim to report and compare the main characteristics and outcomes of patients with PML and several underlying diseases in a referral center in a middle-income country. METHODS: We performed a retrospective cohort study of PML cases admitted to a tertiary care hospital in São Paulo, Brazil during 2000-2022. Demographic and PML-specific variables were recorded. One-year case-fatality rate and factors associated with death were identified using a multivariate Cox proportional hazards regression model. RESULTS: Ninety-nine patients with PML were included. HIV infection (84.8%) and malignancy (14.1%) were the most prevalent underlying conditions. Other predisposing diseases were autoimmune/inflammatory diseases (5.1%) and solid organ transplantation (1.0%). One (1.0%) patient had liver cirrhosis and another (1.0%) patient was previously healthy. Focal motor deficits (64.2%) and gait instability (55.1%) were the most common signs. The one-year case-fatality rate was 52.5% (95% CI 42.2-62.7). The one-year case-fatality rate (95% CI) in patients with or without malignancy (85.7%, 95% CI 57.2-98.2% and 47.1%, 95% CI 36.1-58.2%, respectively) were statistically different (P = 0.009). Crude and adjusted Cox regression models identified malignancy as independently associated with death (adjusted HR = 3.92, 95% CI 1.76-8.73, P = 0.001). CONCLUSIONS: HIV/AIDS was the predisposing condition in 84.8% of PML cases. The one-year case-fatality rate was 52.5% and having a malignancy was independently associated with death. This study reports emerging data on the epidemiology and outcome of PML in a middle-income country.
RESUMO
Background There is uncertainty about the impact of obstructive sleep apnea (OSA) and its phenotypes on cardiovascular disease. Research Question Are OSA and clinical features such as daytime sleepiness associated with incident subclinical coronary atherosclerosis? Study Design and Methods In this prospective community-based cohort study, we performed a sleepiness questionnaire, actigraphy, and home sleep studies at baseline. Coronary artery calcium, CAC (64-slice multi-detector computed tomography) was measured at two different time points throughout the study (baseline, between 2010-2014, and follow-up, between 2016-2018). Incidence of subclinical atherosclerosis was defined as baseline CAC=0 followed by CAC>0 at a 5-year follow-up visit. The association of incident CAC outcome was assessed using logistic regression. Stratified analyses based on excessive daytime sleepiness (EDS) were performed. Results We analyzed 1,956 participants with available CAC scores at baseline (age: 49±8 years; 57.9% women; 32.4% with OSA). In covariate-adjusted analyses (n=1,247, mean follow-up=5.1±0.9 years), we found a significant association between OSA and incidence of subclinical atherosclerosis (OR=1.26; 95% CI 1.06–1.48), with stronger effects among those reporting EDS (OR=1.66; 95% CI: 1.30–2.12; p for interaction=0.028). Interestingly, EDS per se was not associated with any CAC outcome. An exploratory analysis of CAC progression (baseline CAC>0 followed by a numerical increase in scores at follow-up) (n=319) showed a positive association for both OSA (β=1.084; 95% CI: 0.032 to 2.136; p=0.043) and OSA with EDS (β=1.651; 95% CI: 0.208 to 3.094; p=0.025). Interpretation OSA, particularly with EDS, predicts the incidence and progression of CAC. These results support biological plausibility for the increased cardiovascular risk observed among patients with OSA with excessive sleepiness.
RESUMO
Even though darunavir/ritonavir (DRV/r) has high potency and a greater genetic barrier, there are few studies on the long-term effectiveness of DRV/r-based salvage therapy in people living with HIV (PLWH) in low and middle-income countries. This retrospective cohort study, from São Paulo, Brazil, included ART-experienced PLWH aged ≥18 years with virological failure (VF) who had started DRV/r plus an optimized background regimen (OBR) between 2008 and 2012. The proportion of patients with viral load (VL) <50 copies/mL, the improved mean CD4+ T cell count and the factors associated with VF during the 144-week follow-up were assessed. The study included 173 patients with the following characteristics [median (interquartile range)]: age 48 (42 -53) years; CD4+ T cell count, 229 (89 -376) cells/mm3; VL, 4.26 (3.70 -4.74) log10; 6 (4 -7) previous regimens; and 100 (38 -156) months of VF. After 144 weeks, 129 (75%) patients had VL< 50 copies/mL and a mean increase in the CD4+ T cell count of 190 cells/mm3. VL>100,000 copies/mL and poor adherence were associated with VF. DRV/r plus an OBR showed high long-term virological suppression and immunological recovery. VL>100,000 copies/mL and poor adherence were associated with VF at 144 weeks.
